Meta-analyses 1 examining the risks of developing cardiac failure in observational studies and in randomized controlled trials (RCTs) involving patients with arthritis and non-rheumatic disorders was performed. Electronic databases and published bibliographies were systematically searched (1997-2008).
Five case-control studies (4657 patients, 45,862 controls) showed a non-significant association between NSAIDs and cardiac failure in a random effect model (odds ratio (OR) 1.36; 95% CI 0.99-1.85). Two cohort studies (27,418 patient years, 55,367 control years) showed a significant risk of cardiac failure with NSAIDs (relative risk 1.97; 95% CI 1.73-2.25). Six placebo-controlled trials (naproxen, rofecoxib and celecoxib) in non-rheumatic diseases (15,750 patients) showed more cardiac failure with NSAIDs (OR 2.31; 95% CI 1.34, 4.00). Six RCTs comparing conventional NSAIDs and COXIBs in arthritis (62,653 patients) showed no difference in cardiac failure risk (OR 1.14; 95% CI 0.85-1.53).
Observational studies and RCTs all show that NSAIDs increase the risk of cardiac failure. Overall risks are relatively small and are similar with conventional NSAIDs and COXIBs. Pre-existing cardiac failure increases risk.
In the population-based retrospective cohort study 2 the authors identified NSAID-naive individuals aged 66 years or older, who were started on rofecoxib (n=14,583), celecoxib (n=18,908), and non-selective NSAIDs (n=5,391), and randomly selected non-NSAID users as controls (n=100,000).
Relative to non-NSAID users, patients on rofecoxib and non-selective NSAIDS had an increased risk ofadmission for congestive heart failure (adjusted rate ratio 1·8, 95% CI 1·5-2·2, and 1·4, 1·0-1·9, respectively), but not celecoxib (1·0, 0·8-1·3). Compared with celecoxib users, admission was significantly more likely in users of nonselective NSAIDs (1·4, 1·0-1·9) and rofecoxib (1·8, 1·4-2·4). Risk of admission for rofecoxib users was higher than that for non-selective NSAID users (1·5, 1·1-2·1). Of patients with no admission in the past 3 years, only rofecoxib users were at increased risk of subsequent admission relative to controls (1·8, 1·4-2·3).
It was concluded that these findings suggest a higher risk of admission for congestive heart failure in users of rofecoxib and non-selective NSAIDs, but not celecoxib, relative to non-NSAID controls.
Ungprasert and coworkers conducted a systematic review and meta-analysis of observational studies 3 that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of incident HF in NSAID users vs nonusers. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and both subclasses (conventional NSAIDs and highly selective cyclooxygenase-2 inhibitors [COXIBs]) were calculated using a random-effect, generic inverse variance method.
Seven studies with 7 543 805 participants were identified and included in the data analysis. Use ofNSAIDs was associated with a significantly higher risk of developing HF, with a pooled RR of 1.17 (95% CI:1.01-1.36). Subgroup analysis showed a significantly elevated risk among users of conventional NSAIDs (RR:1.35, 95% CI: 1.15-1.57) but not users of COXIBs (RR: 1.03, 95% CI: 0.92-1.16).
Conclusions: A significantly elevated risk of incident HF was observed among users of NSAIDs.
Cohort study 4 with a nested case-control analysis based on the UK General Practice Research Database. Overall, 1396 cases of first hospital admission for non-fatal HF were identified (January 1997 to December 2000) and compared with a random sample of 5000 controls.
The HF incidence rate was 2.7/1000 person years. Prior clinical diagnosis of HF was the main independent risk factor triggering a first HF hospitalisation (relative risk 7.3, 95% confidence interval (CI) 6.1 to 8.8). The risk of a first hospital admission for HF associated with current use of NSAIDs was 1.3 (95% CI 1.1 to 1.6) after controlling for major confounding factors. No effects of dose and duration were found. The relative risk in current users of NSAIDs with prior HF was 8.6 (95% CI 5.3 to 13.8) compared with patients who did not use NSAIDs and without prior clinical diagnosis of HF.
Use of NSAIDs was associated with a small increase in risk of a first hospitalisation for HF. In patients with prior clinical diagnosis of HF, the use of NSAIDs may lead to worsening of pre-existing HF that triggers their hospital admission. This increased risk, although small, may result in considerable public health impact, particularly among the elderly.
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